BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is bei...BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.展开更多
Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying ...Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying the onset of acute elderly asthma as soon as possible and giving the effective treatment is crucial to improve the prognosis. This study was to investigate the significance of fractional exhaled nitric oxide （FeNO） combined with serum procalcitonin （PCT） and C-reactive protein （CRP） in the evaluation of elderly asthma. A total of 120 elderly patients with an acute attack of asthma from July, 2010 to May, 2012 were studied. On presentation, FeNO, serum PCT and CRP concentrations were measured and sputum culture was also performed. The elderly patients were re-evaluated when they had returned to their stable clinical state. The elderly patients were classified into two groups： positive bac- terial culture group （A） and negative bacterial culture group （B）. The results showed that： （1） In patients with an acute exacerbation of asthma, 48 （40%） patients had positive sputum bacterial culture and 72 （60%） had negative sputum bacterial culture. （2） The levels of FeNO in patients with acute exacerbation of asthma were significantly higher than in those with no acute exacerbation state （63.8±24.6 vs. 19±6.5 ppb, P〈0.05）. There was no significant difference in FeNO between group A and group B （P〉0.05）. （3） The levels of PCT and CRP in group A patients with an acute exacerbation of asthma were significantly higher （P〈0.05） than in group B （for PCT： 27.46±9.32 vs. 7.85±3.52 ng/mL; for CRP： 51.25±11.46 vs. 17.11±5.87 mg/L, respectively）. When they had returned to stable clinical state, the levels of PCT and CRP in group A were decreased significantly （P〈0.05）, and those in group B had no significant change （P〉0.05） when compared with the exacerbation group. There were no significant differences in the levels of PCT and CRP between the two groups in non-acute exacerbation state （/9〉0.05）. These results suggest that the increase in FeNO indicates the acute exacerbation of asthma, and the elevation of serum PCT and CRP levels may be associated with bacterial infection.展开更多
Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled...Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled nitric oxide (FeNO) is a candidate biomarker to diagnose ACO. We assessed the effect of an add-on treatment with budesonide/formoterol (BUD/FM) combination in patients with ACO, which was diagnosed by FeNO. Methods: This was a prospective, single-arm, open-label, before and after comparison study. Subjects included 83 patients with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between June and November 2016. All patients fulfilled the GOLD definition of COPD and were receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. After an 8-week run-in period, BUD/FM was added to the patients with FeNO levels of ≥35 ppb, defined as having ACO. For patients receiving LAMA/LABA, BUD/FM was added after the discontinuation of LABA. The modified British Medical Research Council (mMRC) score, COPD assessment test (CAT) score, spirometric indices, forced oscillation parameters, and FeNO were assessed before and after 8 weeks of BUD/ FM add-on treatment. Results: Twenty-four patients (28.9%) had FeNO levels ≥ 35 ppb, and 17 patients completed the study (mean age: 73 years and GOLD I/II/III/IV, 5/10/1/1). The mean CAT scores significantly improved (9.2 to 5.4, p = 0.015) and 10 patients (58.8%) showed ≥2 points improvement, a minimal clinically important difference. The mean FeNO levels significantly decreased from 63.0 to 34.3 ppb (p Conclusions: FeNO-guided treatment with BUD/FM improves symptoms in patients with ACO.展开更多
Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the...Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the inflamed lung. The collection of lung secretions by traditional methods including bronchoalveolar lavage and induced sputum collection are limited by their invasive nature. Exhaled breath condensate (EBC) is a simple and non-invasive technique of collecting fluid samples, which are representative of airway lining fluid. Advances in collection methods and evolving molecular techniques have led to development of more sensitive assays for existing biomarkers and identification of new biomarkers, which can be potentially useful in monitoring lung inflammation. In this review, we present the current understanding of various biomarkers including small molecules (H2O2, pH and nitric oxide related biomarkers), lipid mediators (8-isprostane, leukotrienes and prostaglandins), small proteins (cytokines and chemokines) and nucleic acids (DNA and microRNAs). We also discuss the differential profile of biomarkers in recognizing different patterns of lung inflammation. As the sensitivity of methods of EBC improves, this biofluid will play an increasing role in diagnosis and monitoring of lung diseases.展开更多
Background The airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide （FENO） for th...Background The airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide （FENO） for the regimen adjustment in patients with asthma, the correlation was analyzed between the two parameters and lung function parameter （forced expiratory volume in one second （FEV1））. Methods Sixty-five outpatients with mild to moderate non-exacerbation asthma from Beijing Chao-Yang Hospital were enrolled as treatment group. Combined medications of inhaled corticosteroids plus long-acting beta-2 agonist were administered for one year. Lung function parameters, eosinophil counts in induced sputum, concentration of exhaled nitric oxide and the Asthma Control Test scores were recorded, at regular intervals in the follow-up period. Twenty-one healthy volunteers were enrolled as control group and underwent examination of eosinophil counts in induced sputum, lung function and concentration of exhaled nitric oxide. Results Sixty-three subjects from treatment group completed follow-up period for one year or longer. Mean FEV1 value of the 63 subjects was （2.75±0.54） L at baseline, （2.97±0.56） L and （3.07±0.52） L at month 3 and month 6, respectively, and maintained as （3.14±0.51） L in the following six months. Mean FENO decreased from （61±25） parts per billion （ppb） at baseline to （32±19） ppb at month 3 （P 〈0.05）, and continued to decrease to （22±12） ppb at month 6, the difference being significant when compared to both baseline and control group （（13±8） ppb）. Mean eosinophil counts decreased to （0.032±0.011） ×106/ml at month 3, which was significantly different from baseline （（0.093±_0.023） xl06/ml） and the control group （（0.005±0.003）×l06/ml （both P 〈0.05）. The eosinophil counts in induced sputum correlated positively with concentration of FENO in the first six months （all P 〈0.05）. The concentration of FENO had a significant negative correlation with FEV1 value （all P 〈0.05） in any time point in the follow-up period. The Asthma Control Test scores were 18±5, 19±7, 23±-2, 24±1 and 24±1 at months 1, 3, 6, 9 and 12, respectively, which were significantly different from the score at baseline （14±3） （P 〈0.05 ）. The most rapid clinical effect was observed at the second month after treatment. Conclusion Eosinophil counts in induced sputum and FENO are sensitive parameters to detect airway inflammation and may be useful in evaluating the efficacy of treatment and adjusting medication regimens.展开更多
文摘BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.
基金supported by Fundation of Henan Provincial Medical Science and Technology Research(No.201003098)
文摘Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying the onset of acute elderly asthma as soon as possible and giving the effective treatment is crucial to improve the prognosis. This study was to investigate the significance of fractional exhaled nitric oxide （FeNO） combined with serum procalcitonin （PCT） and C-reactive protein （CRP） in the evaluation of elderly asthma. A total of 120 elderly patients with an acute attack of asthma from July, 2010 to May, 2012 were studied. On presentation, FeNO, serum PCT and CRP concentrations were measured and sputum culture was also performed. The elderly patients were re-evaluated when they had returned to their stable clinical state. The elderly patients were classified into two groups： positive bac- terial culture group （A） and negative bacterial culture group （B）. The results showed that： （1） In patients with an acute exacerbation of asthma, 48 （40%） patients had positive sputum bacterial culture and 72 （60%） had negative sputum bacterial culture. （2） The levels of FeNO in patients with acute exacerbation of asthma were significantly higher than in those with no acute exacerbation state （63.8±24.6 vs. 19±6.5 ppb, P〈0.05）. There was no significant difference in FeNO between group A and group B （P〉0.05）. （3） The levels of PCT and CRP in group A patients with an acute exacerbation of asthma were significantly higher （P〈0.05） than in group B （for PCT： 27.46±9.32 vs. 7.85±3.52 ng/mL; for CRP： 51.25±11.46 vs. 17.11±5.87 mg/L, respectively）. When they had returned to stable clinical state, the levels of PCT and CRP in group A were decreased significantly （P〈0.05）, and those in group B had no significant change （P〉0.05） when compared with the exacerbation group. There were no significant differences in the levels of PCT and CRP between the two groups in non-acute exacerbation state （/9〉0.05）. These results suggest that the increase in FeNO indicates the acute exacerbation of asthma, and the elevation of serum PCT and CRP levels may be associated with bacterial infection.
文摘Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled nitric oxide (FeNO) is a candidate biomarker to diagnose ACO. We assessed the effect of an add-on treatment with budesonide/formoterol (BUD/FM) combination in patients with ACO, which was diagnosed by FeNO. Methods: This was a prospective, single-arm, open-label, before and after comparison study. Subjects included 83 patients with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between June and November 2016. All patients fulfilled the GOLD definition of COPD and were receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. After an 8-week run-in period, BUD/FM was added to the patients with FeNO levels of ≥35 ppb, defined as having ACO. For patients receiving LAMA/LABA, BUD/FM was added after the discontinuation of LABA. The modified British Medical Research Council (mMRC) score, COPD assessment test (CAT) score, spirometric indices, forced oscillation parameters, and FeNO were assessed before and after 8 weeks of BUD/ FM add-on treatment. Results: Twenty-four patients (28.9%) had FeNO levels ≥ 35 ppb, and 17 patients completed the study (mean age: 73 years and GOLD I/II/III/IV, 5/10/1/1). The mean CAT scores significantly improved (9.2 to 5.4, p = 0.015) and 10 patients (58.8%) showed ≥2 points improvement, a minimal clinically important difference. The mean FeNO levels significantly decreased from 63.0 to 34.3 ppb (p Conclusions: FeNO-guided treatment with BUD/FM improves symptoms in patients with ACO.
文摘Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the inflamed lung. The collection of lung secretions by traditional methods including bronchoalveolar lavage and induced sputum collection are limited by their invasive nature. Exhaled breath condensate (EBC) is a simple and non-invasive technique of collecting fluid samples, which are representative of airway lining fluid. Advances in collection methods and evolving molecular techniques have led to development of more sensitive assays for existing biomarkers and identification of new biomarkers, which can be potentially useful in monitoring lung inflammation. In this review, we present the current understanding of various biomarkers including small molecules (H2O2, pH and nitric oxide related biomarkers), lipid mediators (8-isprostane, leukotrienes and prostaglandins), small proteins (cytokines and chemokines) and nucleic acids (DNA and microRNAs). We also discuss the differential profile of biomarkers in recognizing different patterns of lung inflammation. As the sensitivity of methods of EBC improves, this biofluid will play an increasing role in diagnosis and monitoring of lung diseases.
文摘Background The airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide （FENO） for the regimen adjustment in patients with asthma, the correlation was analyzed between the two parameters and lung function parameter （forced expiratory volume in one second （FEV1））. Methods Sixty-five outpatients with mild to moderate non-exacerbation asthma from Beijing Chao-Yang Hospital were enrolled as treatment group. Combined medications of inhaled corticosteroids plus long-acting beta-2 agonist were administered for one year. Lung function parameters, eosinophil counts in induced sputum, concentration of exhaled nitric oxide and the Asthma Control Test scores were recorded, at regular intervals in the follow-up period. Twenty-one healthy volunteers were enrolled as control group and underwent examination of eosinophil counts in induced sputum, lung function and concentration of exhaled nitric oxide. Results Sixty-three subjects from treatment group completed follow-up period for one year or longer. Mean FEV1 value of the 63 subjects was （2.75±0.54） L at baseline, （2.97±0.56） L and （3.07±0.52） L at month 3 and month 6, respectively, and maintained as （3.14±0.51） L in the following six months. Mean FENO decreased from （61±25） parts per billion （ppb） at baseline to （32±19） ppb at month 3 （P 〈0.05）, and continued to decrease to （22±12） ppb at month 6, the difference being significant when compared to both baseline and control group （（13±8） ppb）. Mean eosinophil counts decreased to （0.032±0.011） ×106/ml at month 3, which was significantly different from baseline （（0.093±_0.023） xl06/ml） and the control group （（0.005±0.003）×l06/ml （both P 〈0.05）. The eosinophil counts in induced sputum correlated positively with concentration of FENO in the first six months （all P 〈0.05）. The concentration of FENO had a significant negative correlation with FEV1 value （all P 〈0.05） in any time point in the follow-up period. The Asthma Control Test scores were 18±5, 19±7, 23±-2, 24±1 and 24±1 at months 1, 3, 6, 9 and 12, respectively, which were significantly different from the score at baseline （14±3） （P 〈0.05 ）. The most rapid clinical effect was observed at the second month after treatment. Conclusion Eosinophil counts in induced sputum and FENO are sensitive parameters to detect airway inflammation and may be useful in evaluating the efficacy of treatment and adjusting medication regimens.
